This invention relates to radioactive labeled orgotein.
Orgotein is the non-proprietary name assigned by the United States Adopted Name council to members of a family of water-soluble protein congeners in substantially pure, injectable form, i.e., substantially free from other proteins which are admixed or associated therewith in the sources thereof. U.S. Pat. No. 3,758,682 claims pharmaceutical compositions comprising orgotein. Various uses of orgotein are disclosed in U.S. Pat. Nos. 3,637,441; 3,773,928; 3,773,929; and 3,781,414.
The orgotein metalloproteins are members of a family of protein congeners having a characteristic combination of physical, chemical, biological and pharmacodynamic properties. Each of these congeners is characterized physically by being the isolated, substantially pure form of a globular, buffer and water-soluble protein having a highly compact native conformation which, although heat labile, is stable to heating for several minutes at 65.degree. C. at pH 4-10. Chemically, each is characterized by containing all but 0-2 of the protein aminoacids, a small percentage of carbohydrate, no lipids, 0.1 to 1.0% metal content provided by one to 5 gram atoms per mole of one or more chelated divalent metals having an ionic radius of 0.60 to 1.00 A., and substantially no chelated monovalent metals or those that are cell poisons in the molecule. Table I lists the distribution of aminoacid residues, calculated for a molecular weight of 32,500 of several orgotein congeners.
TABLE I __________________________________________________________________________ AMINO ACID COMPOSITION OF SEVERAL ORGOTEIN CONGENERS [Residues per mole, M.W. = 32,500] __________________________________________________________________________ Red Blood Cells (RBC) Liver, Guinea Aminoacids Beef Beef Sheep Horse Pork Dog Rabbit Rat Pig Chicken Human Range __________________________________________________________________________ Alanine 19 19 18 18 18 16 19 22 22 23 22 16 -23 Arginine 8 8 10 6 8 8 8 7 8 8 8 6-10 Aspartic acid 37 36 35 35 31 29 34 30 34 36 37 29-37 Cystine-1/2 6 6 6 6 6 6 6 6 4 10 8 4-10 Glutamic acid 21 23 22 30 28 30 25 38 29 26 28 21-38 Glycine 53 52 52 51 52 53 54 54 53 56 51 51-56 Histidine 16 16 14 20 16 15 17 20 15 17 14 14-20 Isoleucine 18 18 18 14 16 18 16 16 18 15 17 14-18 Leucine 17 17 17 18 16 16 19 12 17 15 20 12-20 Lysine 22 21 23 26 23 20 21 18 20 21 23 18-26 Methionine 2 2 2 2 2 6 3 4 2 3 1 1-6 Phenylalanine 8 8 7 9 8 8 9 6 8 8 8 6-9 Proline 12 13 15 10 10 10 13 10 12 13 12 10-15 Serine 17 17 14 14 13 20 18 18 18 15 19 13-30 Threonine 26 25 20 16 27 20 21 17 17 18 18 16-27 Tryptophan.sup.1 Nil Nil Nil Nil Nil Nil Nil Nil Nil 1 2 0-2 Tyrosine.sup.2 2 2 2 Nil 4 2 Nil 2 Nil 2 Nil 0-4 Valine 33 32 31 29 29 34 31 35 32 30 30 29-35 Total 317 315 306 304 307 311 315 315 309 317 318 304-318 __________________________________________________________________________ .sup.1 Colorimetric determination .sup.2 Average of amino acid analysis and spectrophotometric determination.
In 1969, the bovine congener of the orgotein protein was discovered to be an enzyme which has the ability to catalyze the destruction of superoxide radicals in a disproportionation into molecular oxygen and hydrogen peroxide. The name "superoxide dismutase" (SOD) was assigned to the protein on the basis of this enzymatic activity. McCord, J. M. and Fridovich, I., J. Biol. Chem. 244, 6049-6055 (1969).
Radioactive-labeled compounds are of great interest as diagnostic agents. Numerous radioactive diagnostic agents contain a radioactive halogen, especially iodine. For example, thyroxine-I.sup.131 is used for thyroid diagnostics, sodium diatrizoate-I.sup.131 for testing the kidney function, the sodium salt of tetrachlorotetraiodofluorescein-I.sup.131 for testing liver function, bromthalein-I.sup.131 for gall bladder examination, N,N'-hydroxydiacetylbis-(3-methylamino-2,4,6-triiodobenzoic acid)-I.sup.131 and N,N'-adipoylbis(3-amino-2,4,6-triiodobenzoic acid)-I.sup.131 for liver and gall bladder examination. The use of radioactively labeled compounds in conjunction with various biochemical processes is also known. Tetrachlorotetraiodofluorescein-I.sup.131, bromthalein-I.sup.131, and gold colloid Au.sup.198 have been employed for the liver function test.
The administration of tritium labeled steroids in humans is also known. Chem. Abstracts, 76, 335g (1972).
For a discussion of the use of radioactive tracers in Medicine, see Winchell, H. S., Hospital Practice, October, 1971, pp. 49-60.
It has now been found that radioactively labeled orgotein is useful in scintigraphy, especially for visualization of the kidneys, since the orgotein is rapidly concentrated therein after parenteral administration.